Standard Chemotherapy Plus Oral Everolimus as Adjuvant Therapy for LAR Breast Cancer Patients: A Randomized, Open-Label, Phase III Trial （POLARIS）
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 904
- 主要终点
- iDFS
研究概览
简要总结
This study enrolled patients with early-stage triple-negative breast cancer who had undergone radical surgery. The postoperative pathology met the TNM staging criteria of pT1c-3N0-3M0, and immunohistochemistry (IHC) results confirmed ER-negative status (IHC showed <1% of tumor cells positive for ER), PR-negative status (IHC showed <1% of tumor cells positive for PR), and HER2-negative status (IHC intensity of 0 or 1+; or IHC intensity of 2+ but with negative in situ hybridization results). Additionally, patients either exhibited high AR expression (IHC showing AR ≥10%) or were classified as the LAR subtype based on digital pathology.
This study plans to prospectively enroll 904 subjects, who will be randomized in a 1:1 ratio after completing standard chemotherapy. They will be allocated to either the standard-of-care (SOC) chemotherapy followed by everolimus group or the SOC-alone group. The study aims to evaluate the efficacy of SOC chemotherapy followed by everolimus versus SOC chemotherapy alone as adjuvant therapy for patients with early-stage radically resected triple-negative breast cancer of the LAR subtype, with the primary endpoint being 3-year invasive disease-free survival (iDFS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must meet **all** of the following inclusion criteria to be enrolled in this study:
- •Female, aged ≥18 years and ≤70 years.
- •ECOG performance status 0-
- •Histologically confirmed invasive triple-negative breast cancer (**definition**: breast cancer with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) all confirmed negative by pathology. Specifically: **ER-negative**: IHC <1%; **PR-negative**: IHC <1%; **HER2-negative**: IHC 0/1+ or IHC 2+ but FISH/CISH negative. Additionally, histology must confirm **high AR expression**: AR IHC ≥10%, **or** digital pathology indicates the LAR subtype.
- •Underwent radical surgery for early-stage breast cancer, with postoperative pathology meeting TNM staging **pT1c-3N0-3M0**.
- •Patients with early-stage breast cancer who have received **at least 4 cycles of neoadjuvant chemotherapy containing anthracycline or taxane agents**, **did not achieve pathological complete response (pCR)**, and **do not carry pathogenic/likely pathogenic germline BRCA1/2 mutations**.
- •Adequate organ function, meeting the following criteria:
- •**Hematology**: HB ≥ 90 g/L (no transfusion within 14 days); ANC ≥ 1.5 × 10⁹/L; PLT ≥ 75 × 10⁹/L.
- •**Biochemistry**: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; serum Cr ≤ 1 × ULN, with creatinine clearance >50 mL/min (Cockcroft-Gault formula).
- •Surgical wound fully healed before study initiation.
- •Females of childbearing potential must use a medically approved contraceptive method during the study treatment and for at least 3 months after the last dose of study drug.
- •The patient voluntarily agrees to participate, signs the informed consent form, demonstrates good compliance, and agrees to follow-up.
排除标准
- •Patients who meet **any** of the following criteria will be excluded from this study:
- •Bilateral breast cancer.
- •Metastatic disease at any site.
- •Patients with cT > 2 cm or positive lymph nodes **and** carrying pathogenic/likely pathogenic germline BRCA1/2 mutations.
- •History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction within the past 6 months, or ventricular arrhythmia.
- •History of clinically significant pulmonary disease, including but not limited to interstitial pneumonia, pneumonia, pulmonary fibrosis, and radiation pneumonitis (except for asymptomatic radiation changes not requiring intervention); or suspected such disease based on screening examinations.
- •History of other malignancies within the past 5 years, excluding cured carcinoma in situ of the cervix, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.
- •Pregnant or lactating women; women of childbearing potential who cannot practice effective contraception.
- •Patients concurrently participating in other clinical trials.
- •Patients with a history of hypersensitivity or known allergy to any component of the study drugs; or patients with a history of allergy to other monoclonal antibodies.
- •Severe or uncontrolled infection.
- •Hypertension that cannot be adequately controlled with antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
- •History of gastrointestinal bleeding within the past 6 months, or clear tendency for gastrointestinal bleeding, such as esophageal varices at risk of bleeding, locally active ulcerative lesions, or fecal occult blood ≥ (++). Patients with fecal occult blood (+) must undergo gastroscopy for further evaluation.
- •Known active HBV or HCV infection (HBV-DNA ≥ 500 IU/mL), or chronic infection with abnormal liver function.
- •Urinalysis showing urine protein ≥ ++, or 24-hour urine protein quantification > 1.0 g.
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to study enrollment.
- •History of drug abuse (psychoactive substances) with inability to abstain, or history of psychiatric disorders.
- •Patients deemed unsuitable for participation by the investigator's judgment.
研究组 & 干预措施
SOC
After completion of standard chemotherapy, undergo observation and follow-up.
SOC-everolimus
After completion of standard chemotherapy, everolimus at a fixed dose of 10 mg orally once daily continuously for a duration of 1 year.
干预措施: Everolimus 10 mg daily (Drug)
结局指标
主要结局
iDFS
时间窗: 3 year
It is defined as the percentage of patients who remain free of invasive disease recurrence, secondary primary invasive cancers, or death from any cause over a 3-year period from randomization or initiation of study treatment.
次要结局
- DFS(3 year)
- DDFS(3year)
- RFS(3 year)
- OS(3 year)
- Safety and Tolerability(3 year)
- Quality of Life score in the per-protocol population(3 year)
研究者
Zhimin Shao
Director of the Department of Breast Surgery, Fudan University Shanghai Cancer Center
Fudan University